Abstract
With most research on interstitial cells (IC) in the bladder being conducted on animal models, it remains unclear whether all structural and functional data on IC from animal models can be translated to the human context. This prompted us to compare the structural and immunohistochemical properties of IC in bladders from mouse, rat and human. Tissue samples were obtained from the bladder dome and subsequently processed for immunohistochemistry and electron microscopy. The ultrastructural properties of IC were compared by means of electron microscopy and IC were additionally characterized with single/double immunohistochemistry/immunofluorescence. Our results reveal a similar organization of the IC network in the upper lamina propria (ULP), the deep lamina propria (DLP) and the detrusor muscle in human, rat and mouse bladders. Furthermore, despite several similarities in IC phenotypes, we also found several obvious inter-species differences in IC, especially in the ULP. Most remarkably in this respect, ULP IC in human bladder predominantly displayed a myoid phenotype with abundant presence of contractile micro-filaments, while those in rat and mouse bladders showed a fibroblast phenotype. In conclusion, the organization of ULP IC, DLP IC and detrusor IC is comparable in human, rat and mouse bladders, although several obvious inter-species differences in IC phenotypes were found. The present data show that translating research data on IC in laboratory animals to the human setting should be carried out with caution.
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Acknowledgements
The authors gratefully acknowledge the excellent technical assistance of Mrs. Sarah Cumps, Mrs. Nathalie Volders, Mrs. Kathleen Van Den Eynde (Leuven), Mrs. Annett Weimann and Mrs. Mandy Berndt-Paetz (Leipzig). TG, JN, IP, FVDA and DDR designed the research study; TG, CS, JN, EV and IP performed the research; TG, JN, DDR, JPT, DD, EV and WE analyzed the data; TG, WE, JPT, JN, TR and DDR wrote the manuscript.
Funding
The Leica Ultracut EM UC7 (AUHA/11/01) and the Tecnai G2 BioTwin electron microscope (AUHA/004) for the EM work were purchased with support of the Hercules Foundation. CS and JN received financial support from the Dr. Siegfried Krüger Stiftung, Leipzig. This study was further supported by the Research Council of the KU Leuven Grant EF/95/010. Dirk De Ridder is a clinical-fundamental researcher of FWO Vlaanderen.
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Thomas Gevaert and Jochen Neuhaus are sharing first authorships
Isabel Pintelon and Dirk De Ridder are sharing last authorships
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Gevaert, T., Neuhaus, J., Vanstreels, E. et al. Comparative study of the organisation and phenotypes of bladder interstitial cells in human, mouse and rat. Cell Tissue Res 370, 403–416 (2017). https://doi.org/10.1007/s00441-017-2694-9
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DOI: https://doi.org/10.1007/s00441-017-2694-9